Water-based extracts from coffee beans skins alleviate inflammation and insulin resistance


When coffee beans are processed and roasted the husk and silverskin of the bean are removed and unused, and often are left behind in fields by coffee producers.

Food science and human nutrition researchers at the University of Illinois are interested in the potential of inflammation-fighting compounds found in the silverskin and husk of coffee beans, not only for their benefits in alleviating chronic disease, but also in adding value to would-be “waste” products from the coffee processing industry.

A recent study, published in Food and Chemical Toxicology, shows that when fat cells of mice were treated with water-based extracts from coffee beans skins, two phenolic compounds – protocatechuic acid and gallic acid – in particular reduced fat-induced inflammation in the cells and improved glucose absorption and insulin sensitivity.

The findings show promise for these bioactive compounds, when consumed as part of the diet, as a strategy for preventing obesity-related chronic illnesses, such as Type 2 diabetes and cardiovascular disease.

“In my lab we have studied bioactive compounds from different foods, and have seen the benefits for the prevention of chronic diseases,” says Elvira Gonzalez de Mejia, professor of food science in the College of Agricultural, Consumer and Environmental Sciences at U of I, and co-author of the study.

“This material from coffee beans is interesting mainly because of its composition. It’s been shown to be non-toxic. And these phenolics have a very high anti-oxidant capacity.”

For the study, the researchers looked at two types of cells, macrophages (immune response cells) and adipocytes (fat cells), and the effect of the combined compounds from the extracts, as well as the individual pure phenolics, on adipogenesis – the production and metabolism of fat cells in the body – and the related hormones. They also looked at the effect on inflammatory pathways.

When obesity-related inflammation is present, the two types of cells work together – stuck in a loop – to increase oxidative stress and interfere with glucose uptake, worsening the situation.

In order to block this loop and prevent chronic disease, the researchers’ goals are to eliminate or reduce as much inflammation as possible in order to allow glucose uptake to be facilitated, as well as to have healthy cells that will produce adequate insulin.

Miguel Rebollo-Hernanz, a visiting scholar in de Mejia’s lab, and lead author of the study, explains how the results provide insights into the mechanism of action of these extracts and pure compounds, and their potential efficacy for future studies in humans or animals.

For the study, the fat cells and immune cells were cultured together to recreate the “real-life” interaction between the two cells.

“We evaluated two extracts and five pure phenolics, and we observed that these phenolics, mainly protocatechuic acid and gallic acid, were able to block this fat accumulation in adipocytes mainly by stimulating lipolysis [the breakdown of fats], but also by generating ‘brown-like’ or ‘beige’ adipocytes,” Rebollo-Hernanz explains.

Significantly, these “brown-like” cells are known as fat burners, and they contain more mitochondria, an important organelle in cells that turns nutrients into energy.

In the study, the researchers observed that some phenolics were able to stimulate browning of the fat cells, increasing the content of mitochondria in adipocytes, or fat cells.

“Macrophages are present in the adipose tissue and when adipose tissue grows excessively, there are interactions that stimulate inflammation and oxidative stress,” Rebollo-Hernanz says. “We saw that these phenolics were able to reduce and decrease the secretion of inflammatory factors, but also decrease oxidative stress.”

When macrophages interact with fat cells, the cells have fewer mitochondria. Having less mitochondria, they lose the capacity of burning lipids.

Using these phenolics, the researchers found that this impact of macrophages on the fat cells was completely blocked. The fat cells maintained their function.

“The compounds we tested were able to inhibit inflammation in the macrophage.

That means inhibiting many markers that produce inflammation to the adipocytes.

Those were blocked,” de Mejia says. “Coming to the adipocytes themselves, we saw inhibition of different markers related to inflammation as well.

Absorption of glucose was improved because the glucose transporters were present. And this went back and forth.

“Now we know that in the presence of these compounds we can reduce inflammation, reduce adipogenesis, and decrease the ‘loop’ that helps the two types of cells grow and develop bad compounds that will negatively affect the whole system,” she adds.

The researchers also stressed the positive impact on the environment of using the coffee bean by-products.

During coffee processing, the bean is separated from the husk, the external outer layer of the bean.

After the bean is roasted, the silverskin layer is separated. “It’s a huge environmental problem because when they separate this husk after processing, it usually stays in the field fermenting, growing mold, and causing problems,” de Mejia explains.

Worldwide 1,160,000 tons of husk are left in fields per year, potentially causing contamination.

Additionally, 43,000 tons of silverskin is produced each year, which, de Mejia adds, may be easier to utilize because it stays with the bean as it is exported to different countries to be roasted.

“Once producers see the value, they will treat these materials as an ingredient instead of a waste,” de Mejia says. “It will require good collaboration between academic institutions, industry, and the public sector to solve this problem, but the market is there for these products.”

The paper, “Phenolic compounds from coffee by-products modulate adipogenesis-related inflammation, mitochondrial dysfunction, and insulin resistance in adipocytes, via insulin/PI3K/AKT signaling pathways,” is published in Food and Chemical Toxicology.

More information: Miguel Rebollo-Hernanz et al, Phenolic compounds from coffee by-products modulate adipogenesis-related inflammation, mitochondrial dysfunction, and insulin resistance in adipocytes, via insulin/PI3K/AKT signaling pathways, Food and Chemical Toxicology (2019). DOI: 10.1016/j.fct.2019.110672

Provided by University of Illinois at Urbana-Champaign 

Coffee is one the most important food commodities in the world. About 60 tropical and subtropical countries produce coffee extensively, and in some cases, it is the main agricultural export product [1].

Brewed coffee is a major contributor to the dietary intake of polyphenols [2]. Besides the long-known stimulant effect, recent research has demonstrated the functional and protective potential of this beverage [3].

Raw coffee beans are rich in bioactive compounds, such as chlorogenic acids, trigonelline (hypoglycemic effects), caffeine, tocopherols and diterpenes.

Caffeine has different biological activities, such as stimulation of the central nervous system, myocardial stimulation, and peripheral vasoconstriction [4]. Phenols are a class of plant compounds with the potential to eliminate free radicals because of their stable structure after free-radical capture as hydroxycinnamic acids, with chlorogenic acids (CGA) and caffeic acid (CA) being the most abundant in coffee [5].

These compounds, found mainly in green coffee, are important and biologically active dietary polyphenols. CGA plays several important therapeutic roles, such as antioxidant, anti-inflammatory, antibacterial, antipyretic, hepato- and neuro-protective activities, and can help prevent retinal degeneration, obesity and hypertension. Likewise, it has been found that CGA can modulate lipid metabolism and glucose in both healthy people and those suffering from genetically related metabolic disorders.

It is speculated that CGA performs crucial roles in lipid and glucose metabolism regulation and thus helps to treat many disorders, such as cardiovascular disease, diabetes and obesity.

It is a free radical scavenger, and a central nervous system stimulator, and has DNA-protective and anticancer functions [6,7,8].

The profiles of these compounds are influenced mainly by genetic aspects, such as species and varieties, and physiological aspects, such as the degree of maturation [9,10]. Differences among species include physical aspects, chemical composition and beverage characteristics. The Robusta (Coffea canephora or C. robusta) variety is used for the production of standard-quality coffees. It produces a drink with pronounced bitterness and has high bioactive compound levels. It is more tolerant of growing heights and climates and is frequently used for instant coffee because of its low cost and high efficiency [11,12].

Roasting is the primary processing that coffee beans undergo. During roasting, the beans develop important flavor characteristics. This process affects the composition of the coffee beans and beverage, also influencing potential food bioactivity due to interactions occurring in the compounds available in the coffee matrix [13].

Epidemiologic data suggest that the high and regular consumption of some foods and beverages reduces the risk of chronic pathologies, such as cancer [14]. Prostate cancer (PCa) is the most frequent in men diagnosed with cancer in Brazil [15], and there is evidence that the acids contained in the coffee act to inhibit cancer [16,17]. The aim of this study was to evaluate and compare the bioactive compounds and antioxidant activity of Robusta coffee bean extracts obtained by spray- and freeze-drying after different roasting processes and their cytotoxic effects on a human prostate carcinoma cell line.

Bioactive Properties of Aqueous Coffee Extract

Sucrose is the main carbohydrate in green coffee. Fructose is one of the main monosaccharides found in coffee beans and its content can vary as a consequence of postharvest processing [21,22]. These sugars were found only in samples of green coffee (Table 2). Sucrose is rapidly destroyed at the initial stage of roasting and is the main source of the aliphatic acids (formic, acetic, glycolic and lactic acids) produced during this process [23]. Therefore, it is not possible to detect sugars in the roasted coffee extracts.

Table 2

Results of sugars and some amino acids for freeze-dried and spray-dried coffee extracts.

Sugars (g/100 g)
Sucrose11.6 ± 0.1 aNDNDND11.8 ± 0.2 aNDNDND
Fructose1.4 ± 0.1 aNDNDND1.3 ± 0.0 aNDNDND
Amino Acids (g/100 g)
Asparagine1.5 ± 0.1 a0.6 ± 0.0 b0.6 ± 0.0 b0.4 ± 0.1 c1.5 ± 0.1 a0.4 ± 0.1 b,c0.6 ± 0.0 b,c0.4 ± 0.1 c
Glutamine3.4 ± 0.2 a2.2 ± 0.0 b2.8 ± 0.1 a,b2.5 ± 0.4 a,b3.4 ± 0.2 a1.5 ± 0.2 c2.8 ± 0.3 d2.6 ± 0.4 e
Histidine0.3 ± 0.0 a0.2 ± 0.0 b0.2 ± 0.0 b0.1 ± 0.0 c0.4 ± 0.1 a0.1 ± 0.0 b,c0.2 ± 0.01 b,c0.1 ± 0.0 c
Arginine1.0 ± 0.0 a0.2 ± 0.0 b0.1 ± 0.0 b0.1 ± 0.0 b1.0 ± 0.0 a0.1 ± 0.0 b0.1 ± 0.0 b0.1 ± 0.0 b
Proline1.1 ± 0.0 a0.6 ± 0.0 b0.6 ± 0.0 b0.5 ± 0.1 b1.2 ± 0.0 a0.4 ± 0.0 b,c0.6 ± 0.7 b0.5 ± 0.1 b
Leucine1.2 ± 0.1 a0.6 ± 0.0 b0.7 ± 0.0 b0.6 ± 0.1 b1.3 ± 0.0 a0.4 ± 0.1 b,c0.8 ± 0.1 b0.6 ± 0.1 b
Phenylalanine0.8 ± 0.0 a0.4 ± 0.0 b0.4 ± 0.0 b0.3 ± 0.0 b0.9 ± 0.0 a0.3 ± 0.4 b0.4 ± 0.1 b0.3 ± 0.0 b

ND: not detected. (a–e) Different letters in the same attribute mean that samples are different (p < 0.05) and same letters indicate the samples are the same (p > 0.05). Abbreviations: GF—green freeze-dried, LF—light roasted freeze-dried, MF—medium roasted freeze-dried, DF—dark roasted freeze-dried, GS—green roasted spray-dried, LS—light roasted spray-dried, MS—medium roasted spray-dried, DS—dark roasted spray-dried.

Regarding the amino acids found in aqueous extracts of Robusta coffee, overall, the amino acid levels dropped by more than half in the roasted samples compared to the green samples (Table 2).

Glutamine was the most abundant amino acid, followed by asparagine, without significant difference between the types of drying. In general, the concentration of amino acids was higher in Robusta than in Arabica variety.

Carbohydrates and amino acids are the main components that contribute to the formation of the typical aroma during roasting. Asparagine and histidine are the main substrates to form acrylamide and 4-methyl imidazole in the roast process, respectively. These substances are potential carcinogens produced by the Maillard reaction [24]. The complete table with the levels of all the amino acids showing their composition and roles were reported by Murkovic and Derler [25].

In the assays of antioxidant activity, the extracts were analyzed at concentrations of 5, 10 and 12.5 mg/L by DPPH assay, Trolox Equivalent Antioxidant Capacity (ABTS/TEAC), Ferric Reducing Ability (FRAP) and Oxygen radical absorbance capacity (ORAC) (Figure 1A,B). The green and light roasted samples presented a similar pattern in the antioxidant analyses. Green and light extracts of freeze-dried Robusta coffee had higher antioxidant potentials in this drying process. In spray-dried extracts, green spray-dried (GS) and light roasted spray-dried (LS) showed the highest potential in comparison with all extracts. The antioxidant capacity observed in roasted coffee extract could be due to the presence of melanoidins, end products of the Maillard reaction [26,27,28].

In ORAC analysis, lower antioxidant activity was observed, with the lowest values observed in spray-dried samples with a minimum value of 20.9 ± 6.7 µM Trolox eq./g and a maximum value in freeze-dried extracts of 510.8 ± 36.9 µM Trolox eq./g. Meanwhile, FRAP results did not show relevant changes in roast types and even in drying processes.

This can occur due to the fact that the ORAC method is performed with the peroxyl radical, which simulates a biological free radical. Some methods, such as FRAP, are based on Fe (III) complex that is a long-living free radical. As expected, these methods can present drawbacks because this synthetic free radical could not be compatible with food matrix natural antioxidants [29]. Studies have shown that no single test can estimate accurately the antioxidant activity in a sample, mainly because standardized methods should evaluate its availability against various oxygen reactive species and/or nitrogen reactive species, such as superoxide anion, hydroxyl (OH) and peroxynitrite, so this requires specific methods for specific radical sources. Thus, the use of different methods is necessary in antioxidant activity measurement and together these techniques could draw a reliable profile of the antioxidant content in a food matrix [30,31].

Changes in the antioxidative capacity of coffee upon roasting are also associated with the degradation of chlorogenic acid, but not necessarily, a reduction in antioxidant activity occurs. Chlorogenic acid fate in roasting can lead to other characteristic roasted products, such as chlorogenic acid lactones, and also minor cinnamic acid derivatives with antioxidant activity as well [27,32,33,34].

The caffeine content was affected by roasting (Table 3). However, the different drying processes did not influence the caffeine content of the extracts. The contents of this alkaloid in the beverage are influenced by the type and also by the process used in its preparation. During roasting, a small amount of caffeine is lost. Robusta coffee has a higher amount of caffeine than the Arabica’s one [35]. Chlorogenic acids and caffeine are found in brewed coffee because they are readily solubilized in hot water. Probably due to the existence of a variation of the content of the various compounds present in this beverage, a strong influence is observed by the processes used in its production chain and preparation for consumption [36].

able 3

Results of caffeine and total phenolic compounds for freeze-dried and spray-dried extracts.

Caffeine (g/100 g)0.3 ± 0.0 a0.2 ± 0.1 b0.2 ± 0.0 b0.1 ± 0.0 c0.4 ± 0.1 a0.2 ± 0.0 b,c0.2 ± 0.0 b,c0.1 ± 0.0 c
Total Phenolic compounds (mg of gallic ac./100 g)3051.1 ± 33.7 a3792.0 ± 13.4 b2177.2 ± 70.8 c2198.7 ± 71.0 c2816.6 ± 19.2 a3046.4 ± 64.0 a1889.0 ± 24.6 d1437.1 ± 17.5 e

(a–e) Different letters in the same attribute mean that samples are different and same letters indicate the samples are the same. Abbreviations: GF—green freeze-dried, LF—light roasted freeze-dried, MF—medium roasted freeze-dried, DF—dark roasted freeze-dried, GS— green freeze-dried, LS—light roasted spray-dried, MS—medium roasted spray-dried, DS—dark roasted spray-dried.

The total phenolic compounds in the light roasted freeze-dried (LF), green freeze-dried (GF), green freeze-dried (GS) and light roasted spray-dried (LS) samples were higher, with values of 3792.0 ± 13.4, 3051.1 ± 33.7, 2816.6 ± 19.2 and 3046.4 ± 64.0 mg gallic acid equivalents/100 g, respectively. There was no significant difference between the GF, GS and LS (p > 0.05). The total content of phenolic compounds was modified in the extracts from roasted beans, and this content was lower in spray-dried samples, where a temperature close to 180 °C was used (Table 3).

Perrone [37] observed the influence of coffee roasting on incorporation of phenolic compounds in melanoidins and their relationship with antioxidant activity. They found values in Arabica coffee from 67.6 mg to 370.3 mg gallic acid equivalents/100 g, varying according to roasting time and cultivar analyzed. The values were lower compared to these in the present study. The composition of extract depends on the solvent used, the quality and the origin of the plant material, storage conditions and pretreatment [38,39].

The contribution of different coffee components to antioxidant activity of the brew is a topic of great interest in literature. Chlorogenic acids are considered to be the major contributors to the antioxidant activity of brewed coffee, followed by melanoidins, which are end products of the Maillard reaction [37,40]. The total chlorogenic acids content of green coffee beans can vary according to species and cultivars, the degree of maturation, agricultural practices, climate and soil [41,42].

The polyphenols undergo chemical modification or degradation upon roasting, and some products of their decomposition, like phenylindans, have high antioxidative activity [32,43]. In addition to the chlorogenic acids, other minor compounds of the chlorogenic acid family have been reported. Trace amounts of diferuloylquinic acids, dimethoxycinamoylquinic acids, caffeoyl-dimethoxycinamoylquinic acids and feruloyl-dimethoxycinamoylquinic acids were identified in Robusta coffee [42,44].

The data show that caffeic acid was the most abundant acid in the dry extracts of Robusta coffee (Figure 2). It is also possible to observe that the roasting process decreased the content of these compounds, but the drying process did not have an influence. The levels of bioactive compounds were lower in the medium and dark roasted samples. The caffeic acid content has a relationship with oxidative properties under thermal conditions. The first steps in the degradation of caffeic acid are related to the formation of decomposition products, which have lower antioxidant capacity when compared to the original molecule [45].


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